Considerable biochemical and pharmacological evidence has accumulated to support the role of histamine as a neurotransmitter in the nervous system, however, the lack of a histological marker for histaminergic neurons has impeded the precise localization of histaminergic neurons in mammalian brain. With an antiserum against histamine, we have the ability to visualize histaminergic neurons at the levels of the light and electron microscopes, and thus begin to acquire a morphological perspective for histamine-containing neurons. In addition to mapping the distribution of histaminergic fibers, terminals and cell bodies by immunohistochemistry, we propose to examine connections of the group of histamine-immunoreactive cell bodies in the hypothalamus by double-labeling cells via histamine-immunoreactivity and the retrograde transport of horse-radish peroxidase. Because of the general involvement of the hypothalamus in the regulation of endocrine and autonomic function, we believe projections of these cells to the median eminence and autonomic nuclei in the brainstem may form the neuronal circuitry whose activation is mimicked in neuropharmacological studies of histamine. Studies of hypothalamic histamine-containing fibers at the ultrastructural level will add insights into the extent to which histamines effects on endocrine function are mediated via neuronal synapses. Finally, we propose to isolate liver and brain histidine decarboylase and raise monoclonal antibodies against the enzymes. The antibodies will be used in immunohistochemistry as an alternate approach to the visualization of histaminergic neurons.